The present invention relates to a multiparticulate dosage form with impeded abuse containing, in addition to one or more active substances having abuse potential (A), optionally at least one physiologically acceptable auxiliary (B), at least one synthetic or natural polymer (C), optionally at least one wax (D) and at least one disintegrating agent (E), with the individual particles of the dosage form having a breaking strength of at least 500 N and a release of the active substance of at least 75% after 45 minutes, and relates to processes for the preparation of the dosage form according to the invention.
A large number of pharmaceutical active substances not only have an outstanding efficacy in their relevant field of application, but also a potential for being abused, i.e. an abuser can use them to produce effects which are not consistent with their intended use. Thus, for example opiates which exhibit an excellent efficacy in controlling severe to extremely severe pain, are frequently abused to induce euphoric states similar to being intoxicated. In particular, active substances which have a psychotropic effect are abused accordingly.
To enable abuse, the corresponding dosage forms, such as tablets or capsules are crushed, for example ground by the abuser, the active substance is extracted from the thus obtained powder using a preferably aqueous liquid and after being optionally filtered through cotton wool or cellulose wadding, the resultant solution is administered parenterally, in particular intravenously. This type of dosage results in an even faster diffusion of the active substance compared to the oral abuse, with the result desired by the abuser, namely the kick. This kick or these intoxication-like, euphoric states are also reached if the powdered dosage form is dosage nasally, i.e. is sniffed.
To prevent these possibilities of abuse, it is proposed in U.S. Pat. No. 4,070,494 to add an agent capable of swelling to the dosage form. This agent swells when water is added to extract the active substance which means that the filtrate separated from the gel contains only a very small amount of active substance.
A corresponding approach for preventing parenteral abuse is also the dosage form of a multi-layer tablet disclosed in U.S. Pat. No. 6,309,668 (=WO 95/20947) which has the active substance with a potential for abuse and at least one gel former respectively separated in different layers.
A further approach for preventing parenteral abuse is disclosed in U.S. Pat. No. 7,214,385 (=WO 03/015531). This document describes a dosage form containing an analgesic opioid and a dye as an aversive agent. The color, released by inadmissible manipulation of the dosage form, is supposed to prevent the abuser from using this manipulated dosage form.
Another known possibility for impeding abuse is to add to the dosage form antagonists of the active substance, for example naloxone or naltrexone in the case of opioids, or to add to the dosage form compounds which lead to physiological deterrent reactions, for example Radix Ipecacuanha=ipecac root.
It is also known to prevent abuse by complicating or preventing the pulverization, necessary for abuse, of the dosage forms by the means usually available to a potential abuser. US 2005/031546 (=DE 103 36 400) discloses appropriately solid dosage forms containing active substance with abuse potential which, when used as intended, ensure the desired therapeutic effect, but from which the active substances cannot be converted by simple pulverization into a form capable of being abused.
These dosage forms secured against abuse are distinguished by a controlled, preferably retarded release of the active substance which has abuse potential. However, a rapid release of the active substance is necessary for numerous therapeutic applications, for example pain relief using active substances with abuse potential.